CD4 is an integral membrane protein of human helper T lymphocytes that serves as an essential component of the receptor for the human immunodeficiency virus (HIV), the causative agent of human immunodeficiency syndrome (AIDS). HIV binding and fusion with the cell are mediated by specific interaction between the external subunit of the viral envelope glycoprotein (gp120) and CD4 on the target cell surface. We are interested in determining the nature of the binding interaction and using this information to develop therapeutic agents. During the past year we have demonstrated that a truncated 180-amino acid fragment of CD4 contains the epitopes for several monoclonal antibodies that block HIV binding and that this CD4 fragment can form a specific complex with gp120. A recombinant fusion protein containing the CD4 binding site and portions of the Pseudomonas exotoxin A selectivity killed cells infected with HIV and/or expressing the HIV envelope protein. This fusion protein has potential for AIDS chemotherapy.